A. Gidaspov, V. Bakharev, Y. Bulychev
Jul 1, 2004
Citations
0
Influential Citations
3
Citations
Journal
Pharmaceutical Chemistry Journal
Abstract
The antitumor activity of various 1,3,5-triazine derivatives has been reported beginning in the 1950s [1]. Most thoroughly studied were the synthesis and antitumor properties of the 1,3,5-triazine derivatives containing ethyleneimine substituents [2 – 5], as well as of the 2,4,6-triamino-1,3,5triazine derivatives with methyl and hydroxymethyl substituents [6 – 10]. Hexamethylmelamine and the related bioactivated product, 2,4,6-tri(methylhydroxymethylamino)-1,3,5-triazine (known as the drug trimelamol), were used for some time in clinical practice for the treatment of ovarian carcinoma, breast tumor, and lung cancer of some types. However, these drugs did not find wide application because of low solubility (hexamethylmelamine) or instability (trimelamol) hindering the development of convenient and effective medicinal forms of these drugs [11, 12]. Another direction in the search for antitumor activity in the series of 1,3,5-triazine was based on the synthesis and biological characterization of aza analogs of the natural pyrimidine nucleosides [13, 14]. Antitumor activity was also observed in some derivatives of 1-aryl-4,6-diamino-2,2-dimethyl-1,2-dihydro-1,3,5-triazines [15, 16]. No data were reported on the cytotoxic activity of 1,3,5-triazines containing one or several polynitromethyl substituents. This study began a series of works in this direction. We have synthesized and characterized with respect to cytotoxic activity a series of previously unreported (2 -R4 -R-1,3,5-triazin-6 -yl)-dinitroethanols and -dinitroethanes with the general formulas